Alagille Syndrome

Alagille syndrome is a rare, inherited disorder. It can affect the liver, heart, eyes, bones, kidneys and nervous system. This disorder is present at birth, although it may not become apparent until later in life.

Often, patients with Alagille syndrome have a distinctive facial appearance.

Patients may have fewer than normal bile ducts in the liver.

A small number of patients (about 15 percent) go on to develop severe liver disease and require liver transplantation.

The disease usually is inherited from one parent. A single copy of the diseased gene (received from either the mother or father) "dominates" the other normal gene and results in this disease.

There is a 50 percent chance a parent with Alagille syndrome will transmit this disorder to his or her child. Family members with Alagille syndrome may be affected very differently by the disorder.

Bile, composed of bilirubin, bile salts, cholesterol and metals such as copper, is produced in the liver and travels through small bile ducts in the liver into one large bile duct. It eventually flows into the intestines. Bile acids are necessary to absorb fat and certain vitamins. When the bile flow is decreased, each of its components builds up in the body, and the body is not able to properly absorb fat and vitamins. This causes a wide range of symptoms.

Symptoms of Alagille syndrome range from mild to severe. Symptoms within the first three months of life often include:

Jaundice (yellowing of skin), usually present at birth

Severe itching (caused by the buildup of bile salt in the body)

Pale, loose or clay-colored stools (this happens because there is little or no bile reaching the intestine to color the bowel movements)

Poor weight gain (due to a lack of bile needed to digest and absorb fat)

Poor growth (even with excellent nutrition, some children with Alagille syndrome are small for age)

Deficiency of vitamins A, D, E and K, which depend on bile acids for absorption; this may result in vision changes, rickets, difficulty with balance and poor clotting of the blood

Heart murmurs, due to narrowing of the blood vessels in the lung (peripheral pulmonary artery stenosis)

Other symptoms that may develop later include:

Jaundice that will not go away

Continued growth and development problems in early childhood

Enlarged liver (feels larger and harder than normal)

Hard, whitish nodules (called xanthomas) that develop in the skin due to cholesterol and fatty deposits; the nodules usually occur in spots of repeated trauma in young children, such as knees and elbows

Urine appears very dark yellow or brown (due to high levels of bilirubin in the bloodstream which pass to the kidneys)

A diagnosis of Alagille syndrome may be made based on genetic testing, or by having certain symptoms. While there are specific findings that indicate Alagille syndrome, you may not have all of the symptoms.

Reduced bile flow is one finding that indicates Alagille syndrome. Symptoms of reduced bile flow include jaundice, itching and cholesterol deposits in the skin.

A liver biopsy may be done to examine the bile ducts and degree of scarring in the liver. Liver function tests are blood tests used to assess the general state of the liver.

Genetic testing is being used more often to identify abnormal genes associated with Alagille syndrome.

Other findings that may indicate Alagille syndrome include:

Heart murmur (due to narrowing of the blood vessel connecting the heart to the lungs)

Bone defects (shape of the bones in the spinal column may look like butterfly wings)

Kidney problems or kidney failure

Distinct physical features, such as a broad forehead, straight nose, deep set eyes, a small, pointed chin, and fingers that are shorter than normal

Problems with the eye – an extra thickening of a line, known as the Schwalbe's line, on the surface of the eye

There is no cure for Alagille syndrome. Management of the disorder is aimed at preventing complications, increasing the flow of bile from the liver, maintaining normal growth and development and reducing blood cholesterol levels.

Medications. Medicine may be used to increase bile flow and to relieve severe itching caused by buildup of bile in the blood and skin. These same medicines may be used to treat high cholesterol levels that cause the hard, whitish nodules that develop in the skin of patients with Alagille syndrome.

Vitamin supplements. Reduced bile flow can lead to difficulty absorbing fat and vitamins from a child's diet. Fat-soluble vitamin supplements (A, D, E and K) may be used.

Baby formula rich in triglyceride. Baby formula rich in a type of fat that can be digested despite reduced bile flow may be used to help with fat absorption in infants.

High-calorie diet. Patients with Alagille syndrome often have difficulty absorbing the calories they eat. To prevent malnutrition and growth failure, a high-calorie diet with a lot of protein may be recommended. A feeding tube that delivers large quantities of nutrients overnight may be used.

Liver transplantation. A small percentage of patients will develop cirrhosis (severe damage to the liver). Liver transplantation is the only option for these patients.

A liver transplant also may be the last resort for patients with severe itching, portal hypertension (caused by excessive scarring in the liver) and severe growth failure that are not responding to medication. Liver transplantation has been used successfully in these cases.